The development of genetic manipulation technology has led to many studies focused on producing large amounts of useful proteins using bacterial and a variety of animals and plants. Host cells for producing large amounts of useful proteins are present, including bacteria such as E. coli, and yeasts such as P. pastoris. Of these host cells, E. coli has been most widely used, and studies thereon have been most frequently conducted (Choi et al., Chem. Eng. Sci., 66: 876, 2006; Lee, Trends Biotechnol., 14:98, 1996).
However, if the useful protein to be produced is larger in size than a naturally occurring protein or is difficult to express, many problems may arise. If the size of a protein is large, translation of the protein may be difficult due to lack of messenger RNA (mRNA), and thus expression of the desired full-length protein may be difficult. In addition, a recombinant protein that is not naturally present in E. coli may be difficult to express, due to proteolysis and RNase-induced degradation of mRNA (GoBringer et al., J Bacteriol., 188: 6816, 2006; Olson et al., PLoS Pathog., 7(2): e1001287, 2011; Jung et al., Biochem Biophys Res Commun., 186(3):1463, 1992; Altman et al., Phil Trans R Soc., 366, 2011; Turrini et al., PLos One., 7(3): e32456, 2012).
Accordingly, the present inventors have made extensive efforts to develop a protein expression system for increasing the production of a difficult-to-express foreign protein, and as a result, have found that, when expression of the rnpA gene (which is a component of ribonuclease P) in a process of expressing the foreign protein by introducing a gene encoding the foreign protein is reduced, expression of the difficult-to-express foreign protein increases, thereby completing the present invention.